Evidence map›Paper›PMID 39110170›Full record

ArticleArchives of toxicology2024

A study of the pharmacokinetics of clozapine and its metabolites by the dynamics of its distribution in the oral fluid of healthy volunteers.

Qianwen Shi, Lele Wang, Qian Zheng, Yefei Pan, Xiaohui Tan, Yao Liu, Shanlin Fu, Ande Ma, Zhiwen Wei, Keming Yun

Abstract read
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In one paragraph

Article in Archives of toxicology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Qianwen Shi *School of Forensic Medicine, Shanxi Medical University, Jinzhong, 030600, Shanxi, China.
Lele Wang *School of Forensic Medicine, Shanxi Medical University, Jinzhong, 030600, Shanxi, China.
Qian Zheng *School of Forensic Medicine, Shanxi Medical University, Jinzhong, 030600, Shanxi, China.
Yefei Pan *Dian Forensic Science Institute, Hangzhou, 310000, Zhejiang, China.
Xiaohui TanThe School of Public Health, Southern Medical University, Guangzhou, 510515, China.
Yao LiuSchool of Forensic Medicine, Shanxi Medical University, Jinzhong, 030600, Shanxi, China.
Shanlin FuCentre for Forensic Science, University of Technology Sydney, Sydney, 2007, Australia.
Ande MaThe School of Public Health, Southern Medical University, Guangzhou, 510515, China.
Zhiwen WeiSchool of Forensic Medicine, Shanxi Medical University, Jinzhong, 030600, Shanxi, China. weizhiwen2000@163.com.
Keming YunSchool of Forensic Medicine, Shanxi Medical University, Jinzhong, 030600, Shanxi, China. yunkeming5142@163.com.

Funding

National Key Research and Development Program of China 2022YFC3300903National Natural Science Foundation of China 82072116National Natural Science Foundation of China 82130056
6 · The paper itself

Abstract

Clozapine (CLZ) -related accidents or crimes are common in the world. Oral fluid drug detection is a convenient measure of dealing with things like that. There has not been any literature reported detailedly the representation rule of clozapine and its metabolites in oral fluid so far. The study aimed to describe the pharmacokinetics of CLZ and its metabolites N-desmethylclozapine and clozapine-N-oxide in human oral fluid after a single 12.5 mg oral dose of CLZ. Twenty-nine volunteers, including 20 males and 9 females, were recruited, and 2 mL oral fluid was collected from each participant at post-consumption time-points of prior (zero), 0.5, 1.5, 3, 5, 8, 12, 24, 36, 51, 82, and 130 h, respectively. Analytes of interest were extracted with solid-phase extraction and analyzed with liquid chromatography tandem mass spectrometry method. Pharmacokinetic parameters were calculated using the pharmacokinetic software DAS according to the non-compartment model. The maximum concentration, the time of maximum concentration, oral clearance, and the elimination half-life of clozapine were 16.57 ± 9.63 ng/mL, 4.53 ± 3.61 h, 57.65 ± 23.77 L/h and 53.58 ± 52.28 h, respectively. The maximum concentration, the time of maximum concentration, and the elimination half-life of the metabolite N-desmethylclozapine were 3.08 ± 1.19 ng/mL, 9.38 ± 9.33 h and 62.67 ± 82.57 h, respectively; of clozapine-N-oxide were 1.15 ± 0.36 ng/mL, 4.53 ± 2.19 h and 19.15 ± 23.11 h, respectively. It was the first study on the pharmacokinetics of CLZ and its metabolites in the oral fluid of Chinese healthy volunteers, and it provided a basis for the therapeutic drug monitoring and toxicological interpretation in clozapine-related cases.

Indexed as

Antipsychotic AgentsClozapineHealthy VolunteersSalivaTandem Mass SpectrometryAdministration, OralAdultChromatography, LiquidFemaleHalf-LifeHumansMaleSolid Phase ExtractionYoung AdultAntipsychotic AgentsClozapineclozapine N-oxidenorclozapineClozapineMetabolitesOral fluidPharmacokinetics

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.